Remodeling the Human Body with Regenerative Medicine and Tissue Engineering

More than a decade since the first patient was treated with ECM, Dr. Stephen Badylak is still working to understand what occurs in the body to make ECM not only become the tissue it rests in, but grow or heal it as well.

Recently, McGowan Institute for Regenerative Medicine deputy director Stephen Badylak, DVM, PhD, MD (pictured), professor in the Department of Surgery, University of Pittsburgh, and director of the Center for Pre-Clinical Tissue Engineering within the McGowan Institute for Regeneration Medicine, and his career medical research efforts with extracellular matrix (ECM) were featured in an article in the Purdue Alumnus, a publication by the Purdue Alumni Association, Inc. “Remodeling the Human Body,” by Tanya Brown, accurately captures Dr. Badylak’s pioneering work into regenerative medicine: his history with ECM, current clinical uses of ECM, and potential future ECM applications.

In the 1980s, Dr. Badylak identified the importance of ECM, which harbors signaling molecules that help direct the development of cells into tissue, during a preclinical experiment in which he used a portion of an intestine to fashion a makeshift aorta for a heart. Not only was the surgery successful, but months later, an examination revealed that the transplanted intestine part had morphed into a vessel that looked much like an aorta. Somehow, it had sensed where it was in the body and had remodeled itself to take on the structural traits of an aorta. There was hardly any scarring. It was during this research period, that Dr. Badylak “stumbled” upon what would become ECM.

“If we had thought that the ECM must be a good scaffolding material, then I would say we were pretty smart, but in fact we were more just lucky,” Dr. Badylak says.

Subsequent research has helped Dr. Badylak and his colleagues understand the mechanisms behind this remarkable tissue remodeling. That research used a layer of intestinal lining called the submucosa, a form of a biological scaffold to support new tissue growth. Dr. Badylak's team found that extracting the submucosa from the intestine and putting patches of it at injury sites triggered a novel healing response: As the implanted matrix material broke down, healthy living tissue, not scar tissue, repaired the damage. Matrix from bladders, liver, and other organs induced a similar reaction.

Today, ECM comes in many forms: freeze-dried, sheet, powder, gel, and its latest form, pillow (a combination sheet and powder product). All of these different kinds provide medical professionals with a vast array of treatment options. Ms. Brown introduces readers to several patients who have benefitted from ECM treatments. Dr. Badylak, in partnership with clinical physicians, has restored the esophagus of cancer patients, regrown the lost finger tips of individuals involved in accidents, and regenerated the muscle tissue of a US wounded warrior. ECM has also been used to replace nervous system tissues, bones, rotator-cuffs, achilles-tendons, and make hernia repairs. Over 2,000,000 patients world-wide have benefitted by some form of this matrix.

More than a decade since the first patient was treated with ECM, Dr. Badylak is still working to understand what occurs in the body to make ECM not only become the tissue it rests in, but grow or heal it as well.

“We now know that it does things like recruit your own stem cells to the site,” he says. “It changes the body’s immune response from inflammatory to constructive remodeling. Rather than harvesting or manipulating stem cells through a complex process outside the body, ECM recruits them from the inside.”

Using ECM kicks the body’s own innate ability to try to reconstruct tissue into high gear, but Dr. Badylak cautions that it is not a fountain of youth or miracle drug. “It’s not going to be in a pill form,” he says. “This is a local application that changes how the body responds to damage.”

“ECM has a large potential as a device coating to improve tissue integration into the wound and to prevent the foreign body reaction and inflammation currently seen with most materials on the market,” Gail Naughton, dean of the School of Management at San Diego State University, CEO of Histogen (a regenerative medicine company), and a longtime colleague of Dr. Badylak. “I also believe that ECM as a whole, not just a collagen, will provide to be an excellent tissue filler and stimulate in-growth of a person’s own cells to more permanently fill the defect and regenerate bone, muscle, and skin.”

Currently in Dr. Badylak’s laboratory, scientists are working to tissue engineer organs; currently the focus is to learn how to decellularize livers by perfusing them with solutions optimized to remove all the cells from the liver tissue while retaining the three-dimensional organ matrix. Recellularization of the liver scaffold then begins. By placing a patient’s own liver cells into a three-dimensional bioscaffold, it may be possible to create new functional liver tissue for patients with end-stage liver disease.